Blood dialyzer

ABSTRACT

A hemodialysis apparatus that carries out hemodialysis treatment by measuring or calculating the blood volume or its volume change as a blood indication level, and by controlling dialysis conditions according to said target blood indication level, wherein the chronological course of said blood indication level is defined as a target control line, and the primary blood volume (BV 0 ) can be calculated as blood indication level. In the former part of the dialysis operation, the water removal is controlled so that the circulating blood volume in the body approach to the standard blood volume (BV st) with the use of said target control line. After the water removal of the former part of the dialysis operation, when the circulating blood volume in the body attains the standard blood volume (BV st), the latter part of the dialysis operation is started. In said latter part of the dialysis operation, the water removal operation is performed by substantively maintaining said standard blood volume (BV st).

TECHNICAL FIELD

[0001] The present invention relates to a blood treatment apparatus,especially to a hemodialysis apparatus which can control water removalconditions and water removal speed so as to prevent excessive waterremoval and also lack of water removal in the contrary, which occurfrequently during hemodialysis.

BACKGROUND ART

[0002] For treating patients with impaired kidney function, treatmentsby purifying blood by dialysis or filtration via semipermeable membranehave been provided conventionally. As for this apparatus, it isimportant to appropriately maintain the blood volume circulating in thepatient body, to perform safe and effective blood purification. A rapidor excessive water removal will decrease excessively patient's bloodcirculating volume, and it may cause reduction of blood pressure, shockor the like. On the contrary, if the water removal is slow, it will takea long time for blood purification, and if sufficient water removalcannot be made, there is a fear that hypertension, heart failure or thelike can occur. Therefore, a hemodialysis apparatus performing waterremoval by monitoring patient's blood condition has been developed. Forexample, in Japanese Laid-Open Patent Publication No. 6-83723, anestimating apparatus which estimates the body fluid condition with aHematocrit meter, and a controlling apparatus which controls the bloodpump or ultra pressure by the output of said estimating apparatus aredescribed. Concerning this apparatus, it is convenient as the waterremoval is controlled directly according to the measured body fluidcondition, but on the other hand, as the water removal is controlleddirectly by the measured value, in case the result of the measuringmeans is not accurate or a trouble happens, it may cause a significantproblem. Therefore, in such feed-forward control, generally, a separateline independent from the control line is disposed and a safetymechanism is loaded on said line. However, the apparatus becomescomplicated when an independent line or safety mechanism is disposed andthe operation becomes difficult. Furthermore, the cost of the apparatuswill rise. Therefore, a simple apparatus as described in JapaneseLaid-Open Patent Application No. 9-149935 was also developed. In otherwords, while monitoring the patient's blood condition, an alarm isringed depending to the condition, and the water removal pump isstopped. However, this apparatus only recognizes if the water removalcontrol is performed under the same control condition at the time of theinitiation of dialysis, by comparing with the blood concentrationmeasured before the initiation of dialysis, and it is not possible toperform adequate water removal to each patent. Furthermore, if the waterremoval is not performed according to the condition, the operator has toadjust each time the water removal volume or fluid replacement volume.Thus, even though it was safe, it was complicated and the human cost washigh. Moreover, as for said apparatus, a means for measuring the bloodcondition is disposed on the line at the vein fluid side of the bloodcycle, the blood condition after having passed the blood treatmentmachine (dialyser) is measured, thus it may not reflect the patient'sdirect blood condition.

[0003] To provide a blood treatment apparatus which have solved theproblems mentioned above, that is, to provide a convenient apparatus ata low cost by making a structure wherein each patient's blood conditionis monitored, enabling to perform blood treatment adequate to eachpatient chronologically, by not imposing much burden to the operatorduring its use, and by making the construction of the blood treatmentapparatus simple, the present inventors provided a blood treatmentapparatus (Japanese Laid-Open Patent Application No. 11-22175),comprising a blood measuring means for measuring blood parameters; aworking unit for performing blood treatment; and a controlling unitcontrolling the working unit to perform blood treatment under prescribedblood treatment condition, wherein the controlling unit indicates thechange of the blood treatment condition to the working unit, by settinga blood indication region determined beforehand against the patientblood indication level obtained with said blood measuring means,according to the chronological transition of said blood indication levelin said blood indication region. Furthermore, the present inventors haveimproved said blood treatment apparatus (Japanese Laid-Open PatentApplication No. 11-22175), and proposed a blood treatment apparatus(Japanese Laid-Open Patent Application No. 2001-540), wherein bymonitoring each patient's blood condition, the condition of hemodialysisadequate to each patient chronologically, especially the water removalspeed can be easily changed and defined. Said blood treatment apparatus(Japanese Laid-Open Patent Application No. 2001-540) is a hemodialysisapparatus comprising at least:(A) a blood measuring means for measuringblood parameter, (B) a working unit for performing blood treatment; and(C) a controlling unit for controlling the working unit to perform bloodtreatment under prescribed blood treatment condition; wherein thehemodialysis apparatus has a mechanism for controlling the water removalspeed, and the controlling unit (C) incorporates the blood indicatinglevel obtained from the patients' samples by the blood measuring means(A), monitoring if it transits or not within the defined range definedbeforehand of blood indication level (hereinafter also referred to asdefined range of blood indication level), and when said blood indicationlevel being the target to control deviates from said range definedbeforehand, the water removal speed of the working unit (B) can bechanged at a speed rate defined beforehand.

[0004] As for the hemodialysis apparatus mentioned above, it waspossible to manage surely the blood indication level at each pointduring hemodialysis treatment, but because it was necessary to definethe region of the target blood indication level at each point, theoperation was complicated. Furthermore, as the defined blood indicationlevel was designated as a range, as long as a blood indication levelexists within the defined range, even it is at the absolute edge of therange, the control mechanism of the hemodialysis apparatus would notwork. Therefore, in case the blood indication level actually measured isslightly missing the point from the target, there was a fear that thecontrol would be delayed. Furthermore, as for said apparatus, minutedetails were defined in each region, and the control is carried outaccording to these, the physiological water removal adequate to eachpatient was difficult to be carried out. On the contrary, when the waterremoval mild to the living body is intended to be carried out, ithappened that the water removal volume which was determined beforehand,can not be attained.

DISCLOSURE OF THE INVENTION

[0005] The object of the present invention is to provide a hemodialysisapparatus that can achieve the following effects:

[0006] (1) The control mechanism is simple, and there is little risk ofmisoperation or out-of-control.

[0007] (2) As there is no need of difficult installation or unnecessaryoperation, the operator can easily operate without difficulty.

[0008] (3) As the control is carried out rapidly and finely, the bloodvolume can be transited fairly during the hemodialysis.

[0009] The present invention provides a hemodialysis apparatus thatcarries out hemodialysis treatment by measuring or calculating the bloodvolume or its volume change as an indication level (hereinafter alsocalled as blood indication level), and by controlling dialysisconditions according to said blood indication level, wherein thechronological course of said target blood indication level is defined asthe target control line, the water removal is controlled with the use ofsaid target control line so that the blood volume circulating in thebody approach to the standard blood volume (BV st) in the former part ofthe dialysis (hereinafter also called as control in the former part ofdialysis operation), the latter part of the dialysis is started when theblood volume circulating in the body attains the standard blood volume(BV st) by the water removal carried out during said former part of thedialysis, and the water removal operation is controlled by maintainingsubstantively said standard blood volume (BV st) in the latter part ofthe dialysis (hereinafter also called as controlling

in the latter part of dialysis operation). Thus, the technical objectmentioned above was solved.

[0010] As said blood indication level, an optional level can be used aslong as it shows the blood volume circulating in the patient, and ΔBV, %ΔBV and the like obtained from BV level (Blood Volume) level, % BV,Hematocrit level can be exemplified. The definition of these parameters,and their calculating formulae are described hereinafter.

[0011] The control of the water removal speed in the former part of thedialysis operation of the hemodialysis apparatus with the use of saidtarget control line is performed by using the blood indication levelmeasured at each measurement point; and the target blood indicationlevel showed by said target control line at the next measurement pointof each measurement point.

[0012] The control of the water removal speed in the former part of thedialysis operation of the hemodialysis apparatus with the use of saidtarget control line can be calculated according to each blood indicationlevel of two adjacent measurement points; the water removal speed usedbetween the two measurement points mentioned above; the blood indicationlevel at the time of the initiation of the hemodialysis; and the targetblood indication level determined by said target control line at thenext measurement point of the two measurement points mentioned above.

[0013] Concretely, said control can be carried out by using thefollowing formula (n).

BV ₀{−(% ΔBV _(n−1′)−% ΔBV _(n′))+(% ΔBV_(n′)−% ΔBV_(n+1))}+UFR _(n)×T=UFR _(n+1) ×T  (n)

[0014] (wherein BV₀ is the blood volume at the time of the initiation ofdialysis (hereinafter also referred as primary blood volume); % ΔBV_(n′)is the ratio of the blood volume change at an optional selectedmeasurement point (n) in the former part of the dialysis operation; %ΔBV_(n−1′) is the ratio of the blood volume change at the previousmeasurement point of the selected measurement point (n) in the formerpart of the dialysis operation; % ΔBV_(n+1) is the ratio of the bloodvolume change determined by said target control line at a measurementpoint (n+1), the next measurement point of the measurement point (n); Tis the measurement time; UFR_(n) is the water removal speed at theselected measurement point in the former part of the dialysis operation;and UFR_(n+1) is the water removal speed defined when the control towardthe working unit is carried out, to attain the target blood indicationlevel at a measurement point (n+1), the next measurement point of themeasurement point (n), respectively.)

[0015] Said formula (n) is calculated as follows:

[0016] When the BV level at the time of the initiation of dialysis isset as BV₀ (primary blood volume), at each measurement point in theformer part of the dialysis operation, for example, relational formulaeas follows are obtained between BV level, PPR and UFR at the first andsecond measurement point.

[0017] 1st Measurement Point

BV ₀{(100%−% ΔBV ₁)−(100%−% ΔBV ₂)}=PRR ₁ −UFR ₁

BV ₀(−% ΔBV _(1′)+% ΔBV _(2′))/T=PRR ₁ −UFR ₁  (1)

[0018] 2nd Measurement Point

BV ₀(−% ΔBV _(2′)+% ΔBV ₃)/T=PRR ₂ −UFR ₂  (2)

[0019] Here, BV₀, % ΔBV_(1′), % ΔBV_(2′) and T show the BV level at thetime of the initiation of dialysis, the ratio of the BV volume change atthe first or second measurement point and the elapsed time of dialysis,respectively. Moreover, % ΔBV₃ is determined by the target control line.

[0020] Similar relations are also obtained at each optional measurementpoints, (n−1) or (n), as it is shown in the following relationalformulae.

[0021] (n−1)th Measurement Point

BV ₀(−% ΔBV _(n−1′)+% ΔBV _(n′))/T=PRR _(n−1) −UFR _(n−1)

[0022] (n)th Measurement Point

BV ₀(−% ΔBV _(n′)+% ΔBV _(n+1))/T=PRR _(n) −UFR _(n)

[0023] By subtracting said formula (2) from said formula (1), thefollowing formula (3) is obtained.

BV ₀{(% ΔBV _(1′)−% ΔBV _(2′))−(% ΔBV _(2′)−% ΔBV ₃)}/T=PRR ₁ −PRR ₂+UFR ₂ −UFR ₁  (3)

[0024] When it is hypothecated there is no difference between PRR₁ andPRR₂, that is the distance between the measurement points are defined tobe short so as the patient's PPR is not changed substantively at eachmeasurement point, the first and second terms in the right side aredeleted. Thus, the following formula (4) is obtained.

BV ₀{−(% ΔBV _(1′)−% ΔBV _(2′))+(% ΔBV _(2′)−% ΔBV ₃)}/T+UFR ₁ =UFR₂  (4)

[0025] In this formula, % ΔBV₃ is the target level at the nextmeasurement point, and is a level for the blood indication level toapproach by carrying out the control. Furthermore, UFR₂ is the waterremoval speed to define so that the blood indication level at the nextmeasurement point approaches the target level mentioned above. Here,BV₀, % ΔBV_(1′), % ΔBV_(2′), T are well known as the BV level at thetime of the initiation of dialysis, the ratio of the blood volume changeat the first or second measurement point, and the elapsed time ofdialysis, respectively. Moreover, UFR₁ is also well known as the waterremoval speed from the first measurement point to the second measurementpoint. Therefore, if % ΔBV₃, which is the target ratio of the BV volumechange is specified, the water removal speed being a dialysis conditioncan be calculated with the formula (4). The target BV level can bedetermined by the target control line, from the measurement point. Onthe contrary, if the hemodialysis treatment is carried out with thatwater removal speed, the BV level at the next measurement point canapproach the target level, that is the target control line.

[0026] When describing the above formula for an optional measurementpoint (n), it is shown as the following formula (n), and as describedabove, the water removal speed to be defined so that the bloodindication level approaches the target at the next point is determinedby the BV volume change at the two measurement points; the water removalspeed between the two measurement points; the measurement level of thedialysis time T; and the blood indication level defined at the nextmeasurement point of the two measurement points mentioned above,determined according to the target control line of said blood indicationlevel.

BV ₀{−(% ΔBV _(n−1′)−% ΔBV _(n′))+(% ΔBV _(n′−% Δ) BV _(n+1))}/T+UFR_(n) =UFR _(n+1)  (n)

[0027] In said formula, BV₀ is the blood volume at the time of theinitiation of dialysis operation; % ΔBV_(n′) is the ratio of the bloodvolume change at an optional selected measurement point (n) in theformer part of the dialysis; % ΔBV_(n−1′) is the ratio of the bloodvolume change at the previous measurement point of an optional selectedmeasurement point (n) in the former part of the dialysis operation; %ΔBV_(n+1) is the ratio of the blood volume change defined at ameasurement point to carry out feed-forward control in the former partof the dialysis operation (next measurement point of measurement point(n)); T is the measurement time; UFR_(n) is the water removal speed atthe selected measurement point in the former part of the dialysisoperation; and UFR_(n+1) is the water removal speed defined at the nextmeasurement point from the selected measurement point (n) in the formerpart of the dialysis operation, when the control is carried out towardthe working unit, to attain the target blood indication level,respectively. However, to obtain said formulae (4) and (n), thecondition that “there is no difference between the PRRs at eachmeasurement point”, which was hypothecated to derive these formulae, isan assumption, and to meet this condition, it is important that thedistance between each measurement point (ΔT) is defined to be short sothat there is no difference between the PRRs. Moreover, as for thiscontrolling method, errors to the control may occur due to errors of BV₀at the time of the initiation of dialysis, control delay and otherfactors, but in the actual control, the control is ensured by definingthe water removal speed at each point (measurement point).

[0028] In other words, as for the water removal operation in the formerpart of the dialysis operation mentioned above, as it is describedabove, the distance between each measurement point is defined to beshort and the water removal speed is defined each time, the errorsoccurring substantively cause no problems.

[0029] The water removal is performed by controlling the water removalspeed with a controlling means as mentioned above, and when the bloodvolume circulating in the body approaches the standard blood volume, thedialysis operation of the latter part of the dialysis operation isstarted. When the dialysis operation of the latter part of the dialysisoperation is started, the remaining water removal volume of the targetwater removal volume is measured or calculated, and the water removalspeed is calculated again to finish removing said water removal volumewithin the target water removal time, and the water removal of thelatter part of the dialysis operation can be performed with said waterremoval speed.

[0030] As for the water removal operation of the hemodialysis apparatusof the present invention, it is preferable to determine beforehand themaximum water removal speed separately for the former part of thedialysis operation and the latter part of the dialysis operation,respectively, and when the water removal speed calculated in the formerpart or latter part of the dialysis operation mentioned above, exceedssaid maximum water removal speed, to control so that the water removalis performed with said maximum water removal speed.

[0031] As for the control of the water removal operation of thehemodialysis apparatus of the present invention, it is preferable todefine separately for the former part and the latter part of thedialysis operation, respectively, a deviated control line (alarm line)to limit the chronological change of the blood indication level within apredetermined range, under said target control line, and when said bloodindication level exceed said deviated control line (alarm line), tocarry out by controlling the working means that carries out thehemodialysis treatment so that the dialysis condition to recover saidblood indication level to be above said deviated control line (alarmline) is performed.

[0032] As for means to recover said blood indication level to be abovesaid deviated control line (alarm line), there is means to stoptemporarily the water removal means.

[0033] In the former part of the dialysis operation, when the means torecover the blood indication level to be above said deviated controlline (alarm line) is performed, and at the time the blood indicationlevel is recovered to be above said deviated control line (alarm line)as a result, the dialysis operation is started again according to thecontrol of the former part of the dialysis operation. Furthermore, inthe latter part of the dialysis operation, when the means to recover theblood indication level to be above said deviated control line (alarmline) is performed, and at the time the blood indication level isrecovered to be above said deviated control line (alarm line) as aresult, the water removal speed is calculated again so that theremaining water removal volume at that time is finished to be removedwithin the target water removal time, and the dialysis operation of thelatter part of the dialysis operation of the latter part of the dialysisoperation is started again with said water removal speed.

[0034] Furthermore, as for the control of the water removal operationfor the hemodialysis apparatus of the present invention, especially inthe latter part of the dialysis operation, it is preferable to enable tocontrol so that the blood indication level is recovered rapidly to beabove said deviated control line (alarm line),

, and in case the blood indication level reaches downward by furtherexceeding said urgent liquid supply line, not only to stop temporarilythe working means that carries out blood treatment as mentioned above,but to use also a water replacement means to inject water replacementinto the body.

[0035] Furthermore, the present inventors have found that as for thecontrol of the water removal speed with the use of said target controlline, the change of the blood volume appears after the change of thewater removal speed (especially at the point when the target controlline drastically changes). Moreover, they have found that when the feedforward control mentioned above is carried out by ignoring saidphenomenon, there is a problem that the control is not stable, and theyhave proposed to solve the problems occurred form said control delay byconsidering said control delay (Japanese patent application 2002-19447),to solve this object. However, as for means proposed above, for examplemeans for calculating the forecast of the dialysis condition necessaryto attain the next target blood indication level (blood volume change)according to the blood indication level at the point the control delaytime has passed, in the controlling method of the water removal speedusing said target control line, can be used when a problem of controldelay as mentioned above occurs in the controlling method of the waterremoval speed which uses said target control line of the presentinvention.

[0036] In the following, parameters concerning blood and bloodindication level and blood used in the hemodialysis apparatus of thepresent invention, will be explained concretely.

[0037] 1. Primary Blood Volume (BV₀)

[0038] It is preferable to use the patient's inherent primary bloodvolume as one of the controlling factors in the former part of thedialysis operation. Said patient's inherent primary blood volume can becalculated for example by the two following methods.

[0039] (1) The First Method for Calculating the Primary Blood Volume(BV₀)

[0040] The first method for calculating the primary blood volume (BV₀)is explained according to FIG. 3.

[0041] At the time of the initiation of dialysis, as the blood volume isnot stable, the water removal is not performed, and only circulationoutside the body is performed. By continuing circulation outside thebody until the blood volume stabilizes, in case the turgor pressureinside the cells is sufficiently high, and the water runs over the cellsand is accumulated up to the cell stroma, it is believed that the bodyfluid (the inflow volume from the cells of FIG. 3) corresponding to theincreased blood volume circulating outside the body (space outside thebody) will move from the cells to the blood vessel. Therefore, it ispossible to obtain the primary blood volume (BV₀) of each patient,according to the following formula (I) with the increased blood volumecirculating outside the body (space outside the body) and % ΔBV_(x).

Primary blood volume (BV ₀)=increased blood volume circulating outsidethe body (space outside the body)/% ΔBV _(x)  (I)

[0042] (% ΔBV_(x) is the ratio of the blood volume change when onlycirculation outside the body is performed without performing waterremoval.)

[0043] (2) The Second Method for Calculating the Primary Blood Volume(BV₀)

[0044] The primary blood volume (BV₀) of each patient can be obtainedalso by the following method. Said second calculating method isexplained according to FIG. 4.

[0045] By using the hemodialysis apparatus which controls dialysisconditions according to the blood indication level, only circulationoutside the body is performed without performing water removal, at thetime of the initiation of dialysis as shown in FIG. 4, said circulationoutside the body is continued until the blood volume (BV) levelstabilizes, and when the blood volume (BV) level becomes stable,dialysis accompanied by water removal is initiated, and at the same timeas said dialysis is initiated, the water removal is performed with acertain time ΔT (within the time PRR does not change), and with acertain water removal speed (water removal speed A), and thus ΔBV_(A),which is the volume change of said BV level is calculated. Then, thewater removal is performed for the same time as said certain time ΔTwith a different water removal speed (water removal speed B), and thus,ΔBV_(B) which is the volume change of said BV level, is calculated.Thus, BV₀ can be calculated by using said ΔBV_(A), said ΔBV_(B), waterremoval speed A and water removal speed B.

[0046] The primary blood volume (BV₀) of each patient calculated by saidsecond method, can be calculated concretely according to the followingformula (II).

BV ₀=(water removal speed A−water removal speed B)/(−ΔBV _(A) %+ΔBV _(B)%)×ΔT  (II)

[0047] Said formula can be calculated as follows. The calculating methodis explained according to FIG. 4.

ΔBV/ΔT=PRR−UFR

−ΔBV _(A) /ΔT+ΔBV _(B) /ΔT=water removal speed A−water removal speed B

ΔBV _(A) =ΔBV ₀·% ΔBV _(A)

ΔBV _(B) =ΔBV ₀·% ΔBV_(B)

BV ₀ /ΔT(−% ΔBV _(A)+% ΔBV _(B))=water removal speed A−water removalspeed B

BV ₀ /ΔT=(water removal speed A−water removal speed B)/(−% ΔBV_(A)+%ΔBV_(B))

[0048] As for the hemodialysis apparatus of the present invention, it ispreferable that it is a constitution that enables to carry out controlwith the use of blood indication level, wherein the target BV % iscalculated automatically according to the following formula with the useof the primary blood volume (BV₀) of each patient calculated asmentioned above, and the standard blood volume (BV st) which is definedbeforehand by doctors and the like.

Target BV %=standard blood volume(BV st)/primary blood volume(BV ₀)×100

[0049] Meanwhile, said standard blood volume (BV st) is a level of theblood volume (BV st) which the patient would have if healthy, definedbeforehand by doctors and the like by considering factors that mightinfluence the human blood volume, for example the patient's age, sex,body height and the like.

[0050] In the meantime, the calculating method of said primary bloodvolume (BV₀) of the present invention is, as it is clear from itscalculating method, it is not limited to the hemodialysis apparatuscontrolling the water removal operation by dividing the dialysisoperation to the former and latter part, and it is widely acceptable aslong as it is a hemodialysis apparatus that carries out hemodialysistreatment by measuring or calculating the blood volume or its volumechange as the blood indication level to control the dialysis conditionaccording to said blood indication level.

[0051] 2. Definition of the Blood Indication Level Being the BloodVolume or its Volume Change and its Calculating Formula

[0052] (1) BV Level

[0053] BV level is the abbreviation of Blood Volume level and is thecirculating blood volume index which is the indication level to checkthe condition of the circulating blood volume of each patient.

[0054] (2) ΔBV Level

[0055] It is the BV volume change, and it is calculated by the followingformula.

ΔBV[BV volume change]=(Ht at the time of the initiation of dialysis/Htat the time of measurement)−1

[0056] Said Ht is the abbreviation of Hematocrit showing the bulk ratioof red corpuscle in the whole blood.

[0057] (3) % ΔBV

[0058] It is the ratio of the blood volume change, and as shown in thefollowing formula, the ΔBV level at the time of measurement is dividedby BV₀ which is the BV level at the time of the initiation of dialysisand is expressed in percentage.

ΔBV %=ΔBV/BV ₀×100

[0059] (4) BV %

[0060] It is calculated by dividing the BV level at the time ofmeasurement by BV₀ at the time of the initiation of dialysis and isexpressed in percentage.

BV %=BV level at the time of measurement/BV ₀×100

[0061] 3. Definition of Other Parameters of Blood and Their CalculatingFormula

[0062] (1) Definition of PRR

[0063] PRR is an abbreviation for Plasma Refilling Rate, and is definedas speed of the blood plasma refilling from the body to the bloodvessel, and shows the patient's water removal ability at each point.

[0064] (2) Formula for calculating PRR

[0065] PPR is calculated with the following formula:

PRR _(n) −UFR _(n) =ΔBV _(n) /T _(n)

[0066] [wherein PRR_(n) is the Plasma Refilling Rate at an optionalselected measurement point (n), UFR_(n) is the water removal speed at anoptional selected measurement point (n), ΔBV_(n) is the blood volumechange at an optional selected measurement point (n), T_(n) is theelapsed time until an optional selected measurement point (n), and UFRis the water removal speed, respectively.]

[0067] Hereinafter, the target control line, the data line and theestimated control line used in the hemodialysis apparatus of the presentinvention will be explained.

[0068] The longitudinal axis of FIG. 2 is % ΔBV level, and thehorizontal axis shows the elapsed time form the initiation of dialysis.

[0069] (1) Target Control Line:

[0070] It is shown by a hatched line A in the former part of thedialysis in FIG. 1 and in FIG. 2, and by a horizontal line D in thelatter part of dialysis. According to this target control line of FIG.1, in the former part of the dialysis operation, a dialysis operation,for example water removal, which decreases the blood volume reasonablyto the body is performed, and in the latter part of dialysis operation,a dialysis operation, for example water removal, which maintains theblood volume suitable to each patient according to the target controlline, that is, to maintain the standard blood volume substantivelyconstant is performed. Therefore, this target control line is anindication of the chronological course or the chronological target levelof the blood indication level. In the meantime, said target control lineis defined before dialysis by doctors and the like, and its angle ofgradient is determined by the relation with the target water removalvolume.

[0071] (2) Data Line and Estimated Control Line

[0072] It will be explained according to FIGS. 1 and 2. The data line Bis the ratio of the blood volume change composed with data level of theblood indication level of % ΔBV_(1′), ΔBV_(2′) and the like. Theestimated control line near by the target control line A is determinedas follows: by using the blood indication level according to themeasurement levels such as BV, ΔBV or % ΔBV and the like at themeasurement point (controlling point); and the target blood indicationlevel shown by said target control line A at the next measurement point(controlling point), the dialysis conditions (for example, the waterremoval speed) to attain the target blood indication level at the nextmeasurement point (controlling point) is calculated, and thehemodialysis treatment is carried out under this calculated dialysisconditions (for example, the water removal speed), to attain the nextmeasurement point (controlling point). As a result, the data line Bwhich will likely slip away from the target control line A, will becorrected by the dialysis conditions newly defined at every measurementpoint (controlling point), and therefore become the estimated controlline C, which transits along said target control line A.

[0073] (3) Deviated Control Line (Alarm Line) and Urgent Liquid SupplyLine

[0074] The hatched line downward sloping shown beneath the targetcontrol line in the former part of the dialysis operation, and thehorizontal line in the latter part of the dialysis operation in FIG. 1,is the deviated control line (alarm line) E to function as a deviatedcontrol line (alarm line). Furthermore, the horizontal line definedunder the deviated control line (alarm line) E in the latter part of thedialysis operation is the urgent liquid supply line F.

[0075] In case dialysis operation is carried out under the control ofthe hemodialysis apparatus of the present invention, in case the bloodindication level actually measured in the former and latter part of thedialysis operation exceeds said deviated control line (alarm line) E, itis preferable to adapt an emergency control, and for example in theformer part of the dialysis operation, it is preferable to adapt anemergency control different from the feed-forward control which usessaid target control line. For example, as it is shown in the graph inFIG. 1, in case the data line showing the transition of the data leveldeviates beneath the alarm line E, the water removal means such as waterremoval pump and the like should be stopped, or in case the data linedeviates beneath the urgent liquid supply line F, if necessary, a fluidreplacement to the patient using a fluid replacement pump is performedby priority before carrying out the control by feed-forward.

[0076] As mentioned above, the hemodialysis apparatus of the presentaspect does not only have the function to approach the blood indicationlevel to the target, but in case (the blood indication level is)deviated in a dangerous region, it is possible to ensure the safety ofthe patient by preferentially operating the emergency control. Moreover,the defined water removal speed is shown in the bottom half of the graphin FIG. 1.

[0077] The hemodialysis apparatus of the present invention stops thewater removal means such as water removal pump and the like by usingsaid deviated control line (alarm line) E or urgent liquid supply lineF, or if necessary performs a fluid replacement to the patient using afluid replacement pump by priority, also in the latter part of dialysisoperation, as described above. Therefore, the hemodialysis apparatus ofthe present invention does not only have the function to approach easilythe blood indication level of the hemodialysis to the target or thestandard blood volume in the former part of the dialysis operation, butin the former part of the dialysis operation and/or in the latter partof the dialysis operation, in case (the blood indication level is)deviated in a dangerous region, it is possible to ensure the safety ofthe patient by preferentially operating the emergency control.

[0078] In the latter part of the dialysis operation, at the time thatthe water removal volume that was planned to be removed in the formerpart of the dialysis operation was removed, the water removal control ofthe latter part of the dialysis operation is started. At this time, thewater removal speed is calculated to finish removing the remaining waterremoval volume within the target water removal time, and the waterremoval is performed with said water removal speed. However, in casesaid water removal speed exceed the maximum water removal speed linedefined for the latter part of the dialysis operation, the hemodialysisis carried out with the maximum water removal speed, as for the formerpart of the dialysis operation.

INDUSTRIAL APPLICABILITY

[0079] By using the hemodialysis apparatus of the present invention,excellent effects such as (1)-(3), as follows, can be obtained.

[0080] (1) The control mechanism is simple, and there is little risk ofmisoperation or out-of-control.

[0081] (2) As there is no need of difficult installation or unnecessaryoperation, the operator can easily operate without difficulty.

[0082] (3) As the control is carried out rapidly and finely, the bloodvolume can be transited fairly during the hemodialysis.

BRIEF DESCRIPTION OF DRAWINGS

[0083]FIG. 1 is a figure explaining the controlling method of the entirewater removal operation of the blood treatment apparatus.

[0084]FIG. 2 is a figure showing the control in the former part of thewater removal operation of the blood treatment apparatus. In FIG. 1, (a)is the period performing only circulation outside the body withoutperforming water removal, (b) is the water removal period at the time ofthe initiation of the water removal, (c), (d), (e), (f), (g), (h), (i),(j), (k), (l), (m), (n), (o) and (p) are water removal speed determinedwith the use of said target control line, alarm line E and maximum waterremoval line G or H, used in the corresponding period. In FIG. 2, %ΔBV_(1′), % ΔBV_(2′), % ΔBV_(3′), % ΔBV_(4′), and % ΔBV_(5′) are theratio of the blood volume change measured at the measurement point 1, 2,3, 4 and 5; % ΔBV₁, % ΔBV₂, % ΔBV₃, % ΔBV₄, and % ΔBV₅ are the ratio ofthe blood volume change determined by the target control line at themeasurement point 1, 2, 3, 4 and 5. Further, ΔT is the interval ofmeasurement time between each measurement point. Moreover, A is thecontrol line (former part), B is the data line, C is the estimatedcontrol line, D is the control line (latter part), E is the deviatedcontrol line (alarm line), F is the urgent liquid supply line, G is themaximum water removal speed line, and H is the maximum water removalspeed line, respectively.

[0085]FIG. 3 is a figure explaining the first calculating method of theprimary blood volume (BV₀).

[0086]FIG. 4 is a figure explaining the second calculating method of theprimary blood volume (BV₀).

BEST MODE OF CARRYING OUT THE INVENTION 1. EXAMPLE 1

[0087] The first method for calculating the primary blood volume (BV₀)is explained according to FIG. 3.

[0088] When starting dialysis, as the BV level was unstable, the waterremoval was not performed at the time of the initiation of dialysis(water removal speed is 0), and only circulation outside the body wasperformed. The blood volume level increased gradually, and after a fixedamount of time, the blood volume stabilized at a constant maximum value.At this time, the hemodialysis apparatus was reset, and the dialysisoperation with water removal was started. The primary blood volume (BV₀)of each patient was obtained from said maximum level of BV, and n % BVlevel, which is the increased blood volume outside the body by usingformula (I). Then, the target BV % was automatically calculated fromsaid primary blood volume (BV₀) of each patient and the standard bloodvolume defined beforehand by doctors and the like, as mentioned above.

2. EXAMPLE 2

[0089] The second method for calculating the primary blood volume (BV₀)is explained according to FIG. 4.

[0090] As Example 1, when starting dialysis, as the blood volume wasunstable, the water removal was not performed at the time of theinitiation of the dialysis (water removal speed is 0), and onlycirculation outside the body was performed. The blood volume levelincreased gradually, and after a fixed amount of time, the blood volumestabilized at a constant maximum value. At this time, the water removalwas performed during a fixed amount of time (within time that PRR doesnot change), at a constant water removal speed (water removal speed A),% ΔBV₁ which is the ratio of the volume change of that BV level iscalculated. Then, the water removal is performed during the same time asthe fixed amount of time mentioned above, with a different water removalspeed (water removal speed B), and % ΔBV₂ which is the ratio of thevolume change of that BV level is calculated. Thus, the patient'sinherent primary blood volume level is easily obtained with the use ofsaid % ΔBV₁, % ΔBV₂, water removal speed A and water removal speed B,according to said formula (II). The target BV % is automaticallycalculated as in Example 1 mentioned above.

3. EXAMPLE 3

[0091] Embodiments of Control for Dialysis Operation

[0092] The embodiments of control for dialysis operation of thehemodialysis apparatus of the present invention is explained accordingto FIG. 1. In the bottom half of FIG. 1, the defined water removal speedis shown.

[0093] As it is shown in FIG. 1, the maximum water removal speed line Gand H are defined in the former and latter part of the dialysisoperation, in the bottom half of FIG. 1, the defined water removal speed(or the history) in the former and latter part of the dialysis operationare shown.

[0094] Former Part of the Dialysis Operation

[0095] (1) Start of Dialysis

[0096] When starting dialysis, as the BV level is unstable, the waterremoval is not performed at the time of the initiation of dialysis(water removal speed is 0), only circulation outside the body isperformed, and it is waited for the time interval to pass until the BVlevel stabilizes (period a).

[0097] (2) The Time of the Initiation of the measurement

[0098] After the BV value stabilizes, the hemodialysis apparatus isreset and the measurement is started again. At this time, during thewater removal time b at the time of the initiation of measurement shownin FIG. 1, the patient's primary blood volume (BV₀) is obtainedaccording to Example 2. Furthermore, this patient's primary blood volume(BV₀) can be obtained according to Example 1 mentioned above, after theBV level stabilizes at the start of dialysis mentioned in above (1),with the use of the variation level of the blood indication level insaid circulation outside the body, and the increased blood volume levelcirculating outside the body.

[0099] The control of the water removal means by feed-forward controlaccording to said target control line is started, according to the waterremoval speed adapted to obtain the primary blood volume in the example2 mentioned above, and each % ΔBV which occurred at that time. Among thewater removal speed (c)-(i) in the former part of the dialysis operationdetermined with the control method mentioned above, the water removalspeed d and h in the former part of the dialysis operation exceed themaximum water removal speed line G, therefore the maximum water removalspeed is adapted. In the meantime, when the water removal speed exceedsthe maximum water removal speed line, it is most preferable to adapt themaximum water removal speed as said water removal speed, but it may be awater removal speed less than the maximum water removal speed. Moreover,as the data level of the blood volume or the blood volume change duringdialysis at water removal speed (f), becomes less than that of the alarmline, the water removal speed is set f=0 (that is, water removal is notperformed).

[0100] (3) Restart of the Water Removal

[0101] In the former part of the dialysis operation, when the bloodvolume or the blood volume change becomes less than the alarm level, thewater removal is stopped (water removal speed f=0), but when the bloodvolume or the blood volume change exceeds the control line as a resultof the termination of water removal, the water removal is started again.As for the primary water removal speed of the control at the time ofstarting again, the water removal is performed with the water removalspeed predicated by the method mentioned above. At the time when thewater removal volume predicted to be removed in the former part of thedialysis operation is removed and the standard blood volume approaches,or at the time when the ratio of the blood volume (% BV) becomes theobject blood volume ratio (object % BV), the control of water removal ofthe latter part of dialysis operation is started.

[0102] (4) Latter Part of Dialysis Operation

[0103] The water removal speed is calculated to finish removing theremaining water removal volume within the target water removal time, andthe water removal is performed with said water removal speed. Whenperforming water removal with this water removal speed, the waterremoval is stopped in case the blood volume or the blood volume changebecomes less than said alarm level. When the blood indication levelattains downward by exceeding the urgent liquid supply line definedbeneath said deviated control line (alarm line), not only the workingmeans that carries out blood treatment as mentioned above is stoppedtemporarily, but the blood indication level is recovered rapidly to beabove said deviated control line (alarm line) by using the liquid supplymeans to inject liquid supply inside the body together. For example,when the water removal is performed with the water removal speed (j),the blood volume or the blood volume change became less than said alarmlevel. Therefore, the water removal at the next controlling point isstopped, and the water removal speed (k) was set to 0.

[0104] Moreover, as a result of termination of said water removal, theactual blood volume change ΔBV level have been recovered to be abovesaid alarm level, the water removal speed is calculated so that theremaining water removal volume at that controlling point is finished tobe removed within the target water removal time (determined waterremoval volume), and the water removal is performed with said determinedwater removal speed (1). By performing the water removal with saiddetermined water removal speed (1), the actual ΔBV level becomes lessthan said alarm level again. Therefore, the water removal at the nextcontrolling point is stopped and the water removal speed (m) was set to0. Furthermore, as a result of termination of said water removal, theactual ΔBV level have been recovered to be above the control line, thewater removal speed is calculated so that the remaining water removalvolume at that controlling point is finished to be removed within thetarget water removal time (determined water removal volume), and thewater removal is performed with said determined water removal speed (n).However, as said determined water removal speed (n) exceeds the maximumwater removal speed line H, the maximum water removal speed was adaptedas the actual water removal speed. As the target water removal volumewas not finished to be removed by the end of the target water removaltime, the water removal was performed with the maximum water removalspeed up to the target removal volume, and the dialysis was finished.

1. A hemodialysis apparatus that carries out hemodialysis treatment bymeasuring or calculating the blood volume or its volume change as ablood indication level, and by controlling dialysis conditions accordingto said blood indication level, wherein the chronological course of saidtarget blood indication level is defined as a target control line, thewater removal is controlled with the use of said target control line sothat the blood volume circulating in the body approach to the standardblood volume (BV st) in the former part of the dialysis operation, thelatter part of the dialysis operation is started when the blood volumecirculating in the body attains the standard blood volume (BV st) by thewater removal carried out during said former part of the dialysisoperation, and the water removal operation is controlled by maintainingsubstantively said standard blood volume (BV st) in said latter part ofthe dialysis.
 2. A hemodialysis apparatus that carries out hemodialysistreatment by measuring or calculating the blood volume or its volumechange as a blood indication level, and by controlling dialysisconditions according to said blood indication level, wherein thehemodialysis apparatus is constituted so that the chronological courseof said target blood indication level is defined as a target controlline, the water removal is not performed at the time of the initiationof the dialysis, and only circulation outside the body is performed,said circulation outside the body is continued until the blood volumestabilizes, and that the primary blood volume (hereinafter also referredas BV₀) of each patient can be calculated by the variation level of theblood indication level at that time and the increased blood volumecirculating outside the body.
 3. The hemodialysis apparatus according toclaim 2, wherein the primary blood volume (BV₀) is calculated accordingto the following formula (I): Primary blood volume (BV ₀)=increasedblood volume circulating outside the body(space outside the body)/%ΔBV_(x)  (I) (% ΔBV_(x) is the ratio of the blood volume change whenonly circulation outside the body is performed without performing waterremoval.)
 4. The hemodialysis apparatus according to claim 2, whereinthe apparatus is constituted so that the water removal is not performedat the time of the initiation of the dialysis, and only circulationoutside the body is performed, said circulation outside the body iscontinued until the blood volume stabilizes, the dialysis with waterremoval is started at the time when the blood volume stabilizes, % ΔBV1which is the ratio of said blood volume change is calculated byperforming water removal in a fixed amount of time (within a time thatPRR does not change) at a constant water removal speed; then % ΔBV₂which is the ratio of that blood volume change is calculated byperforming water removal during the same period as said fixed amount oftime with a different water removal speed (water removal speed B); andthe primary blood volume (BV₀) of each patient can be calculated withthe use of said % ΔBV₁, % ΔBV₂, said water removal speed A and waterremoval speed B.
 5. The hemodialysis apparatus according to claim 4,wherein the primary blood volume of each patient (BV₀) is calculatedaccording to the following formula (II): BV ₀=(water removal speedA−water removal speed B)/(−% ΔBV_(A)+% ΔBV _(B))×ΔT  (II) [% ΔBV_(A) is% ΔBV which generates when the water removal is performed with the waterremoval speed A; Δ % BV_(B) is % ΔBV which generates when the waterremoval is performed with the water removal speed B; ΔT is a fixedamount of time while PRR does not change].
 6. The hemodialysis apparatusaccording to claim 1, wherein the point that the latter part of thedialysis operation starts is the point when % BV becomes the target % BVor % ΔBV.
 7. The hemodialysis apparatus according to claim 1, whereinthe control of the water removal speed with the use of the targetcontrol line in the former part of the dialysis is performed with theuse of the blood indication level measured at each measurement point andthe target blood indication level shown by said target control line atthe next measurement point of each measurement point.
 8. Thehemodialysis apparatus according to claim 1, wherein the control of thewater removal speed with the use of the target control line in theformer part of the dialysis is performed by calculating the waterremoval speed to attain the target blood indication level at the nextmeasurement point, with the use of each blood indication level at thetwo adjacent measurement points, the water removal speed used betweensaid two measurement points, the blood indication level at the time ofthe initiation of the dialysis and the target blood indication leveldetermined by said target control line at the next measurement point ofsaid two measurement points.
 9. The hemodialysis apparatus according toclaim 8, wherein the control of said water removal speed is performedaccording to the following formula (n). BV ₀{−(% ΔBV _(n−1′)−% ΔBV_(n′))+(% ΔBV _(n′)−% ΔBV _(n+1))}/T+UFR _(n) =UFR _(n+1)  (n) (whereinBV₀ is the blood volume at the time of the initiation of dialysis; %ΔBV_(n′) is the ratio of the blood volume change at an optional selectedmeasurement point (n) in the former part of the dialysis operation; %ΔBV_(n−1′) is the ratio of the blood volume change at the previousmeasurement point of the selected measurement point (n) in the formerpart of the dialysis operation; % ΔBV_(n+1) is the ratio of the bloodvolume change determined by said target control line at a measurementpoint (n+1), the next measurement point of the measurement point (n); Tis the measurement time; UFR_(n) is the water removal speed at theselected measurement point in the former part of the dialysis operation;and UFR_(n+1) is the water removal speed defined when the control towardthe working unit is carried out, to attain the target blood indicationlevel at a measurement point (n+1), the next measurement point of themeasurement point (n), respectively, and the distance of eachmeasurement point is defined to be short so that the patient's PRR ateach measurement point does not change substantively.)
 10. Thehemodialysis apparatus according to claim 1, wherein in the latter partof the dialysis operation, when said latter part of the dialysisoperation is started, the water removal speed is calculated again sothat the remaining water removal volume is finished to be removed withinthe target water removal time, and the water removal is performed withsaid water removal speed.
 11. The hemodialysis apparatus according toclaim 1, wherein a maximum water removal speed is defined beforehandseparately for the former and latter part of the dialysis operation, andin case the water removal speed exceeds said maximum water removalspeed, the water removal is performed with said defined maximum waterremoval speed.
 12. The hemodialysis apparatus according to claim 1,wherein a deviated control line (alarm line) to limit the chronologicalchange of the blood indication level within a predetermined rangebeneath said target control line is defined separately for the formerand latter part of the dialysis operation, and the hemodialysisapparatus has a control means of water removal operation to recover saidblood indication level to be above said deviated control line (alarmline) in case said blood indication level exceeds said deviated controlline (alarm line).
 13. The hemodialysis apparatus according to claim 1,wherein an urgent liquid supply line is defined beneath said deviatedcontrol line (alarm line) in the latter part of the dialysis operation,and in case the blood indication level attains downward by exceedingsaid deviated control line (alarm line), the water removal operation isstopped temporarily and the working means is controlled to recover saidblood indication level to be above said deviated control line (alarmline) by using together the liquid supply means to inject liquid supplyinto the body.